We propose to study the mechanisms by which large molecules get across capillary walls and are returned to the bloodstream by the lymphatics. We shall study the characteristics of the capillary wall as a molecular sieve using as test molecules the plasma proteins which are already present, and various exogenous test molecules of comparable molecular size (mostly things like Dextran and gelatin, which have been used clinically as plasma protein substitutes). Chemical and physicochemical procedures will be used to measure and sort out these different molecules in samples of blood plasma and lymph obtained from anesthetized dogs. We shall use animals prepared surgically for chronic collection of lymph in long-term studies of the effects of plasma volume changes on capillary permeability and of lymph removal from the interstititial space.